1. Field of the Invention
The invention relates to devices, methods, and systems that utilize electromagnetic waves within the ultra-high frequency range to provide therapeutic effects for the brain in preventing, ameliorating, or reversing neurologic diseases or disorders which are characterized by abnormal protein aggregation, most notably abnormal brain aggregation/deposition of β-amyloid (Aβ). The invention also relates to devices, methods, and systems for providing cognitive benefits to normal (unimpaired) individuals, as well as to those with age-associated cognitive impairment or sub-normal cognitive function.
2. Brief Description of the Prior Art
A variety of neurologic disorders involve abnormal amyloid protein aggregation or other abnormal protein aggregations in the brain. Primary among amyloid-aggregating disorders is Alzheimer's disease (AD), in which the protein β-amyloid (Aβ) is abnormally produced by neurons and deposited both within neurons in small oligomeric forms, as well as outside of neurons in fibrillary/forms. Many AD researchers believe that brain production and ensuing aggregation of β-amyloid (Aβ) is the root cause of the disease. Thus, any therapeutic that can disaggregate or prevent Aβ aggregation (oligomeric or fibrillary) could be of immense value to protect against or treat AD.
Another amyloid-related neurological disorder is Trisomy 21 (Down's syndrome). Invariably, Down's patients develop Aβ aggregations/plaques (very similar to those of AD), as they age. Moreover, Down's patients become even more cognitively impaired as these brain Aβ aggregations/plaques develop. It is therefore likely that therapeutics aimed at preventing or disaggregating brain Aβ aggregation/deposits could lessen or eliminate the further cognitive impairment experienced b Down's patients in their older age (i.e., generally their 30's).
A third amyloid-related neurological disorder is traumatic brain injury (TBI). The primary/initial injury induced by TBI is largely unavoidable, but triggers secondary brain injury over the hours/days following injury that may be readily treatable. In both humans and animals, a key component to this secondary injury is rapid brain accumulation of the protein β-amyloid (Aβ) in as little as one day after injury. Not surprisingly then, many TBI fatalities have brain Aβ aggregations (deposits) at autopsy. Since Aβ aggregation following TBI appears to be a key mediator of brain tissue loss and resulting cognitive dysfunction, therapeutics aimed at post-TBI suppression of Aβ aggregation could greatly limit secondary TBI injury and provide substantial functional recovery.
Other brain diseases/disorders in which Aβ aggregation/deposition occurs and is thought to be involved in the disease's pathophysiology include Mixed AD/Vascular Dementia, Cerebral Amyloid Angiopathy, Hemorrhagic Stroke, Multi-Infarct Dementia, Cerebral Traumatic Encephalopathy. There are currently no effective therapeutics to treat these conditions, so therapeutics that can disaggregate or prevent Aβ aggregation could have real prophylactic or treatment value.
There are a variety of other neurologic diseases/disorders that are characterized by abnormal aggregation/deposition of non-Aβ proteins, which are thought to aggregation in the same fashion as Aβ—namely, via establishment of hydrogen bonds between monomeric units to form β-pleated sheets. These diseases and their associated abnormally-aggregating protein include Parkinson's Disease (α-synuclein), Lewy Body Dementia (α-synuclein), Fronto-Temporal Lobe Dementia (phosphorylated tau), Huntington's Disease (huntingtin), Amyotrophic Lateral Sclerosis (SOD1) and various Prion Diseases such as Transmissive Sponiform Encephalopathy, Kuru, and Creutzfeldt-Jakob Disease priori protein). Even AD is characterized not only by brain aggregation of Aβ, but also by aggregation of phosphorylated-tau.
Conventional pharmacotherapy has thus far failed to slow or reverse AD adequately, and has minimally impacted the other aforementioned brain disorders characterized by abnormal amyloid aggregation or the aggregation of other abnormal proteins in the brain. There thus exists a need for non-pharmacologic devices, methods, and systems capable of providing effective therapeutic interventions against these disorders—all of which have the common feature of abnormal protein deposition in the brain.
In this regard, there are a variety of “neuromodulatory” approaches against AD that are currently being clinical investigated, including Transcranial Magnetic Treatment (tMT), Transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS). All of these approaches simply stimulate existing neuronal circuitry and have not been demonstrated to affect the AD process (as it is currently understood). As the newest neuromodulatory approach against neurodegenerative diseases, Transcranial Electromagnetic Treatment (TEMT) offers distinct advantages, including deep/global brain treatment and disruption of the AD process. The inventors' preclinical work, beginning with their initial 2010 publication and extended greatly by four succeeding publications, forms the scientific basis for use of TEMT technology, as the invention described below, for the prevention and treatment of numerous neurologic diseases characterized by amyloid and non-amyloid protein aggregation in the brain.
After reviewing an extensive literature, the World Health Organization and other health councils/organizations have concluded that there are no adverse health risks to adults or children associated with electromagnetic fields (EMFs) within the Industry, Science, Medicine (ISM) band between 902-928 MHz, and more broadly between the 850-1900 MHz frequencies utilized by most present-day cell phones. However, there is little data concerning the long-term effects of these EMF frequencies on brain physiology and function. Epidemiologic studies have suggested that occupational (low frequencies around 60 Hz) EMF exposure may increase risk of Alzheimer's Disease (AD), while other studies have found that acute exposure to cell phone (high frequencies of 850-1900 MHz) EMF has essentially no effect, or a limited effect, on cognitive function in normal individuals. To date, no controlled long-term studies of EMF effects on cognitive function have been done in humans or humans with Alzheimer's disease. However, the inventors have performed multiple studies involving transgenic mouse models for AD with EMF frequencies in the ISM band that have clearly shown that long-term EMF treatment to these AD mice results in cognitive protection or reversal of cognitive impairment. In these same animals, they have shown that EMF not only prevents or reverses brain Aβ aggregation, but it also enhances mitochondrial function and increases neuronal activity. These findings are detailed below in the Detailed Description of the Preferred Embodiment.